Topics of current studies include: 1. virulence factors of Cryptococcus neoformans; 2. genetic complementation in Cryptococcus neoformans; 3. yeast-form growth and the viability of yeast cells of Histoplasma capsulatum in vitro; and 4. intrageneric effect of killer toxin produced by Cryptococcus laurentii. The relationship between encapsulation and phenoloxidase activity of Cryptococcus neoformans in the manifestation of virulence for mice was studied by employing the isolates with various combinations of Cap and Mel markers. The isolates with the Cap+ Mel+ phenotype produced fatal infection in 90 to 100% of the animals within 40 days. The isolates with Cap+ Mel- phenotype produced fatal infection after 40 days, and 70 to 90% of the mice survived at least until day 70. Revertants, Cap+ Mel+, were recovered from the mice which died on day 68 after receiving an inoculum of Cap+ Mel- cells. The isolates with phenotypes of Cap- Mel- and Cap- Mel+ not only failed to produce fatal infection but failed to revert to the Cap+ Mel+ type in the mouse brain during the 70 day experimental period. A complementation test was devised for the fungus Cryptococcus neoformans. Complementation was signalled by the growth of prototrophic heterokaryons generated in crosses of the type aB X Ab, where a and b represent any two of the genetic auxotrophic markers. The complementing heterokaryons formed characteristic hyphal colonies. The viability of yeast form of Histoplasma capsulatum has previously been estimated by the use of dye exclusion test. Our study showed that the dye-exclusion test is unreliable for viability estimation and that counting of colony forming units produced on the Histoplasma growth factor medium was the only method which is reproducible as well as reliable. The isolates of Cryptococcus neoformans and Cryptococcus albidus were more sensitive to the killer toxin produced by an isolate of Cryptococcus laurentii than any other species of Cryptococcus.